Regulation of Cell Surface Glycan Expression in Cancer Stem Cells

Cell surface glycans are recognized to be good markers for human pluripotent embryonic stem cells. Typical glycan markers for human embryonic stem cells include SSEA-3, SSEA-4, TRA-1-60 and SSEA-5. Some of these glycans are recently known to be frequently expressed in human cancers, especially in cancer stem cells. Cell surface glycans undergo drastic changes also during malignant transformation, and the glycans which preferentially appear in cancers are clinically utilized as diagnostic markers for human cancers. Such tumor marker glycans include sialyl Lewis A and sialyl Lewis X, expression of which we recently showed to be enhanced in cancer stem-like cells that had undergone epithelial-mesenchymal transition. Sialyl Lewis A was also shown to be expressed in human embryonic stem cells, and to behave as an embryonic stem cell specific marker. Thus, a glycan initially described as a cancer-associated glycan in the cancer research field is now known to be an embryonic stem cell marker, while glycans formerly regarded to be typical embryonic stem cell markers in the embryology field are now shown to be cancer stem cell markers. This suggests the presence of a common induction mechanism for these glycans shared by embryonic stem cells and cancer stem cells. However, the regulatory mechanisms for stem-cell specific glycan expression remain largely unknown. In this chapter we will introduce how glycan-related genes responsible for synthesis of the stem-cell specific glycans are regulated through specific epigenetic modification, by niche-associated microenvironmental factors such as hypoxia, and during a morphogenic process like epithelial-mesenchymal transition.

Keywords: Cancer stem cells, DNA methylation, Dupan-2, Embryonic stem (ES) cells, Epigenetic silencing, Epithelial-mesenchymal transition (EMT), Histone deacetylation, Histone methylation, Hypoxia inducible factor, Selectins, Sialyl Lewis A, Sialyl Lewis X, Siglecs, SLC26A2, SSEA-3, SSEA-4, SSEA-5, ST6GalNAc6, Sulfate transporter, TRA-1-60.